Cellular uptake of DNA-chitosan nanoparticles: The role of clathrin- and caveolae-mediated pathways
Cellular uptake of DNA-chitosan nanoparticles: The role of clathrin- and caveolae-mediated pathways
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DOI：
10.1016/j.ijbiomac.2012.08.016
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发表时间：
2012-12-01
影响因子：
8.2
通讯作者：
Davies, Catharina de L.
中科院分区：
文献类型：
--
作者：
Garaiova, Zuzana;Strand, Sabina P.;Davies, Catharina de L.
基因治疗的成功取决于 DNA 的有效传递，并且需要载体。一种有前途的非病毒载体是壳聚糖。我们通过合成自支化和三糖取代的壳聚糖低聚物 (SBTCO) 来定制壳聚糖，以优化其转染效果，与线性壳聚糖 (LCD) 相比，该低聚物表现出优异的转染功效。这项工作的目的是比较 LCO 和 SBTCO 形成的复合物的细胞摄取和内吞途径。两种复合物均被大多数细胞摄取，但 LCO 的摄取低于 SBTCO 复合物。 LCO 复合物通过网格蛋白依赖性和网格蛋白非依赖性途径内化，而 SBTCO 复合物主要通过网格蛋白非依赖性内吞作用被内化。不同水平的细胞摄取和不同的内吞途径可以解释转染功效的差异。光化学内化显着增加了 LCD 复合物的转染，而 SBTCO 复合物对转染没有影响，这一观察结果支持了这一点。 (C) 2012 Elsevier B.V. 保留所有权利。
The success of gene therapy depends on efficient delivery of DNA and requires a vector. A promising non-viral vector is chitosan. We tailored chitosan to optimize it for transfection by synthesizing self-branched and trisaccharide-substituted chitosan oligomers (SBTCO), which show superior transfection efficacy compared with linear chitosan (LCD). The aim of the work was to compare the cellular uptake and endocytic pathways of polyplexes formed by LCO and SBTCO. Both polyplexes were taken up by the majority of the cells, but the uptake of LCO was lower than SBTCO polyplexes. LCO polyplexes were internalized through both clathrin-dependent and clathrin-independent pathways, whereas SBTCO polyplexes were primarily taken up by clathrin-independent endocytosis. The different level of cellular uptake and the distinct endocytic pathways, may explain the difference in transfection efficacy. This was supported by the observation that photochemical internalization increased the transfection by LCD polyplexes considerably, whereas no effect on transfection was found for SBTCO polyplexes. (C) 2012 Elsevier B.V. All rights reserved.